Determination of Levamisole in Urine by Gas Chromatography-Mass Spectrometry

Abstract

The United States Public Health Service Substance Abuse and Mental Health Services Administration is alerting medical professionals that a substantial percentage of cocaine imported into the United States is adulterated with levamisole, a veterinary pharmaceutical that can cause blood cell disorders such as severe neutropenia and agranulocytosis. Levamisole HCl is the active ingredient in a number of veterinary drugs approved to treat worm infestations in animals. Levamisole HCl was also the active ingredient in a human drug for oral administration approved on June 18, 1990, as adjuvant treatment in combination with fluorouracil after surgical resection in patients with Duke's stage C colon cancer. This drug was withdrawn from the U.S. market around 2000, and it has not been marketed in the U.S. since then. The objective of this study was to develop a method to determine the amount of levamisole in urine samples. The procedure will be provided to state health laboratories as needed to be used in the evaluation of patients that have developed neutropenia or agranulocytosis in the setting of recent cocaine use. A gas chromatography-mass spectrometry method was validated and tested at two different laboratories, and the method limit of detection for levamisole is 1 ng/mL in urine when using a 5-mL sample. Confirmation of the stereoisomer of levamisole was done by high-performance liquid chromatography using a chiral column.

Levamisole-Contaminated Cocaine: An Emergent Cause of Vasculitis and Skin Necrosis

“…The reason why levamisole is added intentionally during the manufacturing process of the cocaine is to potentiate the psychoaffective effects mainly by its stimulant activity due to dopamine release and also because of the similar appearance. It is usually detected by gas chromatography mass spectroscopy technique in urine specimens [9]. The first cases of levamisole-associated vasculitis and agranulocytosis among cocaine users were reported in 2008 in the southwestern United States [8].…”

Amperometric flow-injection determination of the anthelmintic drugs ivermectin and levamisole using electrochemically pretreated boron-doped diamond electrodes

“…Numerous methods have also been described in the literature for the determination of LVM, but mainly using chromatographic techniques coupled with different detectors [16,19,20]. However, as far as we could ascertain, there are only two electroanalytical methods described for the determination of this drug, as reviewed next.…”

Agranulocytosis – Sequelae of Chronic Cocaine Use: Case Series and Literature Review

“…Levamisole-induced production of IL-12 is mediated through Toll-like receptor (TLR)-2 [4]. The adulterant can be detected in urine by gas chromatography-mass spectrometry [5]. …”